The objective of this project is to identify anticaries agents suitable for short-term clinical investigation and to develop methods for assessing these agents. Screening is conducted both in vitro and in animals. The in vitro studies include measurement of the minimal inhibitory concentration and modification of enamel dissolution rate conferred by the test agent. The animal studies measure the effects of an agent on dental caries and plaque. Two recently developed antiseptics, a piperazine derivative and a bispyridine, provided protection against dental caries and plaque similar to that provided by chlorhexidine. Methods used for plaque assessment should consider the agent being tested and the objectives of the study. The fluorescence microscopy method is particularly suitable for studies in which both plaque and caries is being measured.